Di-chloromethyl-propargyl-carbinol



United States Patent DI-CHLOROMETHYL-PROPARGYL-CARBINOL Otto Isler, Basel, and Paul Zeller, Neuallschwil, Switzerland, assignors to Hotlmann-La Roche Inc., Nutley, N. J., a corporation of New Jersey No Drawing. Application June 7, 1954, Serial No. 435,034

Claims priority, application Switzerland June 12, 1953 1 Claim. (Cl. 260-633) The present invention provides a novel propargylcarbinol, i. e. di-chloromethyl-propargyl-carbinol. This compound is pharmacologically active. In particular, it possesses strong hypnotic properties while being of low toxicity. It is thus useful as :a sedative.

The present invention further provides a process for the manufacture of the said di-chloromethyl-propargylcarbinol, which process comprises reacting a propargyl halide, preferably the bromide, by means of a zinc reaction with 1,3-dichloroacetone and hydrolytically decomposing the zinc compound formed.

1,3-dichloroacetone :and propargyl halides are known starting materials. The condensation of the propargyl halide with the ketone is suitably conducted in the presence of an inert solvent, preferably ether or a mixture of ether and benzene. The zinc metal acting as condensation agent may advantageously be present in the form of zinc dust or zinc granules. It is recommended to effect the reaction at a temperature of about 40 C. A suitable mode of procedure consists in adding a mixture of the ketone with the propargyl halide to the zinc metal condens'ation agent, while taking care of excluding any mois- 2,783,282 Patented Feb. 26, 1957 during the reaction is hydrolysed, in the manner usual for such zinc reactions, e. g. by means of dilute acid, of water or of ammonium salt solutions. The propargyl-carbinol thus produced may be purified by distillation.

Example In a vessel equipped with a reflux condenser 11.9 parts by weight of propargyl bromide, 12.7 parts by weight of 1,3-dichloroacetone and 35 parts by weight of dry ether are added, while stirring and under exclusion of moisture, to 10 parts by weight of zinc dust in such a manner as to keep the solvent constantly boiling by the influence of the heat of reaction. After completion of the addition, the reaction mixture is stirred for further 10 minutes, then cooled down to 5 C. and hydrolyzed with 3 N sulfuric acid. The condensation product is taken up in ether, washed with water, dried with calcium chloride, the solvent is evaporated and the residue is fractionated. The main run consists of 10 parts by weight of (ii-chloro- 'methyl-prop-argyl-carbinol of boiling point 64-65 C./ 0.2

min. and n =1.5018.

We claim: Di-chloromethyl-propargyl-carbiuol.

References Cited in the file of this patent UNITED STATES PATENTS 1,841,768 Straus et al. Jan. 19, 1932 2,444,960 Smith et a1. July 13, 1948 2,540,116 Huber e tal. Feb. 6, 1951 OTHER REFERENCES Henbest et -al.: Reformatskii Reactions with Propargyl Bromide, J. Chem. 300., London (1949), pgs. 26962700.

Berger: Medicinal Chemistry, vol. I (1951), pgs. 129-130.

Pan et al.: Effect of halogenation of acetylenic carbinols, J. Pharmacol. Exptl. Therap, vol. 109, pg. 268 1953). 

